Early goal-directed therapy in severe sepsis and septic shock: Insights and comparisons to ProCESS, ProMISe, and ARISE

H. Bryant Nguyen, Anja Kathrin Jaehne, Namita Jayaprakash, Matthew W. Semler, Sara Hegab, Angel Coz Yataco, Geneva Tatem, Dhafer Salem, Steven Moore, Kamran Boka, Jasreen Kaur Gill, Jayna Gardner-Gray, Jacqueline Pflaum, Juan Pablo Domecq, Gina Hurst, Justin B. Belsky, Raymond Fowkes, Ronald B. Elkin, Steven Q. Simpson, Jay L. FalkDaniel J. Singer, Emanuel P. Rivers

Research output: Contribution to journalReview articlepeer-review

125 Scopus citations


Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.

Original languageEnglish (US)
Article number160
JournalCritical Care
Issue number1
StatePublished - Jul 1 2016

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine


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